AIM: Genetic polymorphisms have the potential to influence drug metabolism and vary among ethnic groups. This study evaluated the correlation of genetic polymorphisms with nevirapine pharmacokinetics exposure in Malawians. MATERIALS & METHODS: CYP450 2B6, 2D6, 3A4 and 3A5, ABCB1 and constitutive androstane receptor and pregnane X receptor, were analyzed for polymorphisms in 26 subjects. RESULTS: Allele frequencies (variant) were: CYP2B6 514G>T (0.31) CYP2D6*4 (0.02); CYP2D6*17 (0.35); CYP3A4*1B (0.77); CYP3A5*3 (0.25); ABCB1 2677G>T (0.0), ABCB1 3435C>T (0.21), NR1I3 13711152T>C (0.02), NR1I2 44477T>C (0.10), NR1I2 63396C>T (0.33), NR1I2 6-bp indel (del: 0.17). CYP2B6 516G>T (non-wild-type/wild-type) correlated with nevirapine pharmacokinetic parameters; geometric mean ratios (95% CI): 1.75 (1.27-2.40) for area under the concentration time curve (AUC)(0-12 h), 1.58 (1.03-2.42) for C(0), and 0.53 (0.31-0.91) for clearance. In a multivariable model, nevirapine AUC increased by 1.5% per year of age (p < 0.0001), CYP2B6 516 T allele increased AUC by 92% (p < 0.0001), and CYP3A5*3 decreased AUC by 31% (p = 0.0027). CONCLUSION: Allele frequencies were similar to other sub-Saharan African populations. The T allele for CYP2B6 516 was significantly associated with nevirapine exposure.
AIM: Genetic polymorphisms have the potential to influence drug metabolism and vary among ethnic groups. This study evaluated the correlation of genetic polymorphisms with nevirapine pharmacokinetics exposure in Malawians. MATERIALS & METHODS: CYP450 2B6, 2D6, 3A4 and 3A5, ABCB1 and constitutive androstane receptor and pregnane X receptor, were analyzed for polymorphisms in 26 subjects. RESULTS: Allele frequencies (variant) were: CYP2B6 514G>T (0.31) CYP2D6*4 (0.02); CYP2D6*17 (0.35); CYP3A4*1B (0.77); CYP3A5*3 (0.25); ABCB1 2677G>T (0.0), ABCB1 3435C>T (0.21), NR1I3 13711152T>C (0.02), NR1I2 44477T>C (0.10), NR1I2 63396C>T (0.33), NR1I2 6-bp indel (del: 0.17). CYP2B6 516G>T (non-wild-type/wild-type) correlated with nevirapine pharmacokinetic parameters; geometric mean ratios (95% CI): 1.75 (1.27-2.40) for area under the concentration time curve (AUC)(0-12 h), 1.58 (1.03-2.42) for C(0), and 0.53 (0.31-0.91) for clearance. In a multivariable model, nevirapine AUC increased by 1.5% per year of age (p < 0.0001), CYP2B6 516 T allele increased AUC by 92% (p < 0.0001), and CYP3A5*3 decreased AUC by 31% (p = 0.0027). CONCLUSION: Allele frequencies were similar to other sub-Saharan African populations. The T allele for CYP2B6 516 was significantly associated with nevirapine exposure.
Authors: P Kuehl; J Zhang; Y Lin; J Lamba; M Assem; J Schuetz; P B Watkins; A Daly; S A Wrighton; S D Hall; P Maurel; M Relling; C Brimer; K Yasuda; R Venkataramanan; S Strom; K Thummel; M S Boguski; E Schuetz Journal: Nat Genet Date: 2001-04 Impact factor: 38.330
Authors: Naser L Rezk; Richard R Tidwell; Angela D M Kashuba Journal: J Chromatogr B Analyt Technol Biomed Life Sci Date: 2003-07-05 Impact factor: 3.205
Authors: A I Veldkamp; G J Weverling; J M Lange; J S Montaner; P Reiss; D A Cooper; S Vella; D Hall; J H Beijnen; R M Hoetelmans Journal: AIDS Date: 2001-06-15 Impact factor: 4.177
Authors: David W Haas; Hulin Wu; Haihong Li; Ronald J Bosch; Michael M Lederman; Daniel Kuritzkes; Alan Landay; Elizabeth Connick; Constance Benson; Grant R Wilkinson; Harold Kessler; Richard B Kim Journal: J Acquir Immune Defic Syndr Date: 2003-11-01 Impact factor: 3.731
Authors: Theodora E M S de Vries-Sluijs; Jeanne P Dieleman; Dennis Arts; Alwin D R Huitema; Jos H Beijnen; Martin Schutten; Marchina E van der Ende Journal: Clin Pharmacokinet Date: 2003 Impact factor: 6.447
Authors: Keneuoe Cecilia Nthontho; Andrew Khulekani Ndlovu; Kirthana Sharma; Ishmael Kasvosve; Daniel Louis Hertz; Giacomo Maria Paganotti Journal: Pharmgenomics Pers Med Date: 2022-06-21
Authors: Taimour Langaee; Mohammad H Al-Shaer; Yan Gong; Elizabeth Lima; Sampson Antwi; Anthony Enimil; Albert Dompreh; Hongmei Yang; Wael A Alghamdi; Lubbe Wiesner; Charles A Peloquin; Awewura Kwara Journal: Infect Genet Evol Date: 2021-04-08 Impact factor: 3.342
Authors: Laura Dickinson; Masautso Chaponda; Daniel F Carr; Joep J van Oosterhout; Johnstone Kumwenda; David G Lalloo; Munir Pirmohamed; Robert S Heyderman; Saye H Khoo Journal: Antimicrob Agents Chemother Date: 2013-11-11 Impact factor: 5.191